The Johns Hopkins University School of Medicine

Office of Research Administration733 North BroadwayBRB, Suite 117

Baltimore, MD 21205

United States

The Cebpa Downstream Enhancer as a Key Target of Transformation to Acute Myeloid Leukemia

Background

Acute myeloid leukemia (AML) accounts for 20% of pediatric leukemias, and despite considerable improvements in treatment, has an approximately 50% mortality rate. Mutations in AML can be classified into two categories: type I that stimulate proliferation, and type II that inhibit normal differentiation. C/EBPa, a protein critical for normal maturation of myeloid cells, is decreased in the majority of AML cases. Previously, the Friedman laboratory identified a DNA region encoding a C/EBPa enhancer, which functions to increase its production.

Targeting Abnormal Metabolism in Neuroblastoma

Brain Tumors, Neuroblastoma

Background

We have demonstrated that inhibitors of glutamine metabolism such as DON, acivicin, and Compound 968 effectively kill medulloblastoma cells and prevent the growth of MYC-driven medulloblastoma orthotopic xenografts. NMYC amplified neuroblastoma also shows increased glutamine metabolism. We do not know if inhibitors of glutamine metabolism will effectively kill neuroblastoma cells.

HMGA1-Targeted Nanoparticles as Novel Therapy for Pediatric Leukemias

Leukemia

Background

The high mobility group A1 (HMGA1) protein plays an important in role during embryonic development, but in cancer the HMGA1 gene becomes re-expressed, stimulating stem cell pathways which enables tumors to rapidly proliferate and evade many conventional treatments. HMGA1 is present in high levels in virtually all aggressive cancers studied to date, including pediatric ALL and AML. Together, ALL and AML are two of the leading causes of death for children with cancer.

Targeting Tumor Suppressor MicroRNAs in Pediatric Acute Lymphoblastic Leukemia

Leukemia, Acute Lymphoblastic Leukemia (ALL), Lymphoma

Background

Acute lymphoblastic leukemia (ALL) is the most common form of childhood leukemia and the leading cause of death in children with cancer. While therapy is often curative, ~15% of children will relapse with recurrent disease and poor outcomes. Why some children develop resistant disease remains unclear.

A Developmental Model to Characterize the Epigenetic Origins of the Retinoblastoma Tumor Initiating Cell

Retinoblastoma

Dr. Huo has moved to Levine Children's Hospital in Charlotte, NC

Targeting the Epigenome of Diffuse Intrinsic Pontine Glioma

Brain Tumors, Glioma

Background

Approximately a quarter of children with cancer have tumors of the brain and spinal cord. Unfortunately most children with diffuse intrinsic pontine glioma (DIPG), one type of brain tumor, die within two years of diagnosis. Scientists have not been able to find a cure for this tumor but as science advances, we have slowly gained a better understanding of what makes one tumor different from another and what may be the underlying mechanism that triggers this devastating disease.

Molecular Targeting of FLT3 and Leukemic Stem Cell Pathways in Pediatric AML

Acute Myeloid Leukemia (AML)

Targeting RNA Helicase DDX3 to Treat Recurrent High Grade Sarcoma

Ewing Sarcoma

Background
Current treatments for patients with relapsed sarcomas are ineffective. The best chemotherapy regimens shrink tumors only 40% of the time, without prolonging survival. Effective treatments for these patients are a critical unmet medical need, and new molecularly targeted therapies represent the most promising approach to this difficult problem.

Epigenetic Regulation of T cell Activation and Immunotherapy

Lymphoma

Background

One reason cancer cells grow uncontrollably is because they turn off genetic brakes on growth using a process called DNA methylation. Drugs that block DNA methylation appear to stop cancer from growing and make it more sensitive to other treatments. However, little is known about the impact of these drugs on the normal immune system.

Development of the Next Generation FLT3 Inhibitors for Pediatric AML and Infant ALL - Donald Small, MD, PhD (2012)

Acute Lymphoblastic Leukemia (ALL), Acute Myeloid Leukemia (AML)

Background

Certain visible changes in the chromosomes and mutations in the genes correlate with good or bad prognosis in leukemia. FLT3 is one of the most frequently mutated genes in pediatric AML and also plays an important role in Infant ALL. In both types of pediatric leukemias the FLT3 protein acts as a gas pedal that is permanently pressed to the floor, telling cells to grow out of control. In order to send this signal, FLT3 needs to bind to an energy molecule called ATP.

Alex's Lemonade Stand Foundation for Childhood Cancer